ARC-520 Can Produce Deep and Durable Reductions of Hepatitis B Viral Antigens

齐欢畅2

Arrowhead Late-Breaking Clinical Data Shows that ARC-520 Can Produce Deep and Durable Reductions of Hepatitis B Viral Antigens and DNA

PASADENA, Calif.--(BUSINESS WIRE)-- Arrowhead Research Corporation (NASDAQ: ARWR), a biopharmaceutical company developing targeted RNAi therapeutics, presented data from a Phase 2a clinical study at The AASLD Liver Meeting 2015® demonstrating that ARC-520, its lead drug candidate against chronic hepatitis B infection (HBV), effectively reduced HBV viral antigens derived from cccDNA. HBV surface antigen (HBsAg) was reduced substantially with a maximum reduction of 1.9 logs (99%) and a mean maximum reduction of 1.5 logs (96.8%) in treatment naïve e-antigen (HBeAg)-positive patients. This direct antiviral effect was still evident 57 days after a single dose. These data strongly support advancement of ARC-520, and Arrowhead has initiated multiple studies aimed at producing a functional cure of HBV.

Christopher Anzalone, Ph.D., Arrowhead's president and chief executive officer said, "At AASLD we presented data from our clinical program and from a nonclinical study in chimpanzees. Both of these studies show that ARC-520 can produce deep and durable knockdown of HBV viral antigens. These data give us additional confidence in the program as we move forward with multiple-dose and combination studies of ARC-520, that we hope will lead to host immune reconstitution, HBsAg seroclearance, and functional cure."

Man-Fung Yuen, M.D., Ph.D., chair of gastroenterology and hepatology, The University of Hong Kong, and deputy chief of service, Queen Mary Hospital department of medicine, Hong Kong, and a principal investigator for Arrowhead's Phase 2a clinical study, delivered a late-breaking poster presentation titled, "ARC-520 produces deep and durable knockdown of viral antigens and DNA in a phase II study in patients with chronic hepatitis B".

In this presentation, Dr. Yuen and co-authors show that in the Heparc-2001 clinical study, ARC-520 in combination with entecavir achieved maximum reductions of HBsAg, HBV DNA, HBeAg, and core-related antigen (HBcrAg) of 1.9 logs (99%), 4.3 logs (99.995%), 1.7 logs (98%), and 1.2 logs (93.7%), respectively.

HBeAg-positive, treatment naïve patients achieved consistent reductions in HBsAg with a mean maximal reduction of 1.5 logs (96.8%). ARC-520 caused a direct antiviral effect after a single dose that was still evident after 57 days, which was the last time-point available.

Consistent with findings from Arrowhead's chimpanzee study, also presented at AASLD, variations in viral antigen reduction indicated that patients previously treated with chronic entecavir and patients that were treatment-naive and negative for HBeAg likely had lower levels of cccDNA derived mRNA transcripts. As such, HBeAg-positive treatment naïve patients experienced a greater relative reduction in HBsAg than patients that were HBeAg-negative or treatment experienced. One transitional patient in cohort 7 was HBeAg-positive at baseline and became HBeAg-negative at days 3 to 43. This patient experienced an intermediate response initially, however HBsAg continued to trend downward through day 57, the last time-point available.

In the clinical study, 58 patients with chronic HBV received doses of 1mg/kg - 4 mg/kg of ARC-520 in 7 cohorts. The cohorts varied by ARC-520 dose, HBeAg status, and prior NUC treatment status. The primary objective of the study was to measure the depth and duration of HBsAg reduction in response to a single dose or two doses (cohort 6) of ARC-520 in combination with entecavir. Arrowhead also assessed safety and tolerability and additional secondary and exploratory endpoints.

ARC-520 was well tolerated with no serious adverse events (AE), no dose limiting toxicities, no discontinuations due to medication AEs, and a modest occurrence rate (23%) of AEs that were all deemed unrelated to study drug by the principal investigator. No AE occurred more than once. There were no AEs amongst 10 patients receiving placebo. There was a low occurrence rate of abnormal laboratory tests, with no observed relationship to timing or dose.

Copies of presentation materials can be accessed by visiting the Events section of the company's website at http://ir.arrowheadresearch.com/events.cfm.

newchinabok

能翻译一下否？

guilin2013

还是以前的数据，没什么变化，美国2B的应有结果的了，但还没发布；还有要做多少个2B和多少年2B呢，还有什么时候进入三期呢，看来说2017年底到18年初上市是不太可能的了；还有能否开多个2B进入中国呢？看来如果不来中国内陆做临床的话，3、2年想用上它的药是有点难的了，如果有效，按现在的速度和效率2020能用上就不错了

囧图

其它不说，只提文中一点:对e抗原阳性病人，最高降低1.9log表面抗原（平均降低1.5log表面抗原）。这能算得上“治愈”？！差得远吧！

囧图

文中提到arc520与恩替联合使用，可以降低s抗原，e抗原，HBV-DNA，c抗原数量不等的几个log载量，这也只能说明有一定疗效（联合后，效果到底是谁取得的？恩替还是arc520?）。此文提到function cure的词语，只是一厢情愿！试验数据根本没有功能治愈的底气！

floraho

ARC520 2a实验结果：单剂量停药57天后， HBeAg阳性初治患者得HBsAg显著下降，最高下降99%，平均下降96.8%。
港大玛丽医院的实验表明ARC520和替诺福韦联合用药，HBsAg, HBV DNA, HBeAg, 及 HBcrAg最高分布下降了 1.9 logs (99%), 4.3 logs (99.995%), 1.7 logs (98%), and 1.2 logs (93.7%)。有一位病人在实验第三天仍是HBeAg阳性，第43天转阴。
无明显副作用。23%的患者报告有不良反应？但证明这些与ARC520无关，不是其引起的。

囧图

此药的最好结局:成为干扰素，核苷药的补充。从此，乙肝治疗多了一种选择。效果与现有药处于同等地位。说白了，此药对现有的乙肝药物是一种补充，不是进步！
更不是功能治愈乙肝药。
目前从已经披露试验数据只能支持以上结论。期待新的试验数据…

newchinabok

在好的药，如果停药反弹了，还不是竹蓝打水

bond007

知足吧，能降1.9log，已经算不错的了。表抗200国际单位以内的人，用长效干扰素，转阴几率蛮高的。

齐欢畅2

罗马不是一天建成的。